Complex medical history of a patient with a compound heterozygous mutation in C1QC.

INTRODUCTION: C1q is an essential part of the classical pathway of complement activation. Genetic deficiencies, caused by homozygous mutations in one of the C1q genes, are rare and are strongly associated with development of systemic lupus erythematosus (SLE). Here we describe a C1q-deficient patient with a compound heterozygous mutation. MATERIAL AND METHODS: Serum was analysed with enzyme-linked immunosorbent assay (ELISA) and Western blot for the presence of C1q, and DNA and RNA sequencing was performed to identify the mutations and confirm that these were located on different chromosomes. RESULTS: The medical history of the patient includes SLE diagnosis at age 11 years with cerebral involvement at age 13, various infections, osteonecrosis and hemophagocytic syndrome. Using ELISA and Western blot, we confirmed the absence of C1q in the serum of the patient. Using DNA sequencing, two mutations in the C1QC gene were identified: c.100G > A p.(Gly34Arg) and c.205C > T p.(Arg69X). With RNA sequencing we confirmed that the mutations are located on different chromosomes. DISCUSSION: The patient described in this case report has a compound heterozygous mutation in C1QC resulting in C1q deficiency.

Are serum autoantibodies associated with brain changes in systemic lupus erythematosus? MRI data from the Leiden NP-SLE cohort.

OBJECTIVE: The effect of serum autoantibodies on the brain of systemic lupus erythematosus (SLE) patients remains unclear. We investigated whether serum autoantibodies, individually and assessed in groups, are associated with specific brain-MRI abnormalities or whether these structural changes are associated with other SLE-related or traditional cardiovascular disease risk factors. METHODS: All patients underwent brain 3Tesla-MRI. White matter hyperintensities (WMHs), ischemic lesions, inflammatory-like lesions and cerebral atrophy were scored. Serum autoantibodies analyzed included lupus anticoagulant (LAC), anticardiolipine (aCL) IgG and IgM (first 3 also grouped into antiphospholipid autoantibodies (aPL)), anti-dsDNA, anti-SSA, anti-SSB, anti-RNP, and anti-Sm (the latter 5 grouped into SLE-related autoantibodies). Associations were assessed using logistic regression analysis adjusted for potential confounders. Furthermore, a sensitivity analysis including anti-Beta2 glycoprotein-1 antibodies (anti-ß2GP1) in the aPL group was performed and the potential modification role of the neuropsychiatric clinical status in the model was assessed. RESULTS: 325 patients (mean age 42 years (SD 14), 89% female) were included. The following MRI-brain abnormalities were found: WMHs (71%), lacunar infarcts (21%), gliosis (11%), micro-hemorrhages (5%), large hemorrhages (2%), inflammatory-like lesions (6%) and atrophy (14%). No associations were found between individual or total SLE-related autoantibodies and inflammatory-like lesions. A higher number of positive aPL was associated with lacunar infarcts (OR 1.37 (95%CI 1.02-1.99) and gliosis (OR 2.15 (1.37-3.37)). LAC was associated with lacunar infarcts in white matter (OR 3.38 (1.32-8.68)) and atrophy (OR 2.49 (1.01-6.15)), and aCL IgG with gliosis (OR 2.71 (1.05-7.02)). Among other variables, SLE patients with hypertension presented a higher chance for WMHs (OR 5.61 (2.52-12.48)) and lacunar infarcts in WM (OR 2.52 (1.10-5.74)) and basal ganglia (OR 8.34 (2.19-31.70)), while cumulative SLE-damage was correlated with lacunar infarcts in WM (OR 1.43 (1.07-1.90)), basal ganglia (OR 1.72 (1.18-2.51)) and cerebellum (OR 1.79 (1.33-2.41)). These associations were confirmed in the sensitivity analysis. CONCLUSIONS: Brain abnormalities in SLE represent different underlying pathogenic mechanisms. aPL are associated with ischemic brain changes in SLE, while the presence of SLE-related serum autoantibodies is not related to inflammatory-like lesions. Hypertension and cumulative SLE-damage associate with ischemic MRI-brain changes in SLE, suggesting the importance of accelerated atherosclerosis in this process.

Neuropsychiatric symptoms in systemic lupus erythematosus: impact on quality of life.

Objective Assess quality of life in patients with systemic lupus erythematosus (SLE) presenting with neuropsychiatric symptoms (neuropsychiatric SLE, NPSLE). Methods Quality of life was assessed using the Short-Form 36 item Health Survey (SF-36) in patients visiting the Leiden NPSLE clinic at baseline and at follow-up. SF-36 subscales and summary scores were calculated and compared with quality of life of the general Dutch population and patients with other chronic diseases. Results At baseline, quality of life was assessed in 248 SLE patients, of whom 98 had NPSLE (39.7%). Follow-up data were available for 104 patients (42%), of whom 64 had NPSLE (61.5%). SLE patients presenting neuropsychiatric symptoms showed a significantly reduced quality of life in all subscales of the SF-36. Quality of life at follow-up showed a significant improvement in physical functioning role ( p = 0.001), social functioning ( p = 0.007), vitality ( p = 0.023), mental health ( p = 0.014) and mental component score ( p = 0.042) in patients with neuropsychiatric symptoms not attributed to SLE, but no significant improvement was seen in patients with NPSLE. Conclusion Quality of life is significantly reduced in patients with SLE presenting neuropsychiatric symptoms compared with the general population and patients with other chronic diseases. Quality of life remains considerably impaired at follow-up. Our results illustrate the need for biopsychosocial care in patients with SLE and neuropsychiatric symptoms.

Outcomes of neuropsychiatric events in systemic lupus erythematosus based on clinical phenotypes; prospective data from the Leiden NP SLE cohort.

Objective The objective of this study was to assess whether clinical and patient's reported outcomes are associated with a different pathophysiological origin of neuropsychiatric events presenting in systemic lupus erythematosus. Methods A total of 232 neuropsychiatric events presenting in 131 systemic lupus erythematosus patients were included. Neuropsychiatric systemic lupus erythematosus diagnosis was established per event by multidisciplinary evaluation. All neuropsychiatric events were divided according to a suspected underlying pathophysiological process into one of the following: non-neuropsychiatric systemic lupus erythematosus related, inflammatory and ischaemic neuropsychiatric systemic lupus erythematosus. The clinical outcome of all neuropsychiatric events was determined by a physician-completed four-point Likert scale. Health-related quality of life was measured with the subscales of the patient-generated Short Form 36 (SF-36) health survey questionnaire. The change between scores at paired visits of all domain scores, mental component summary (SF-36 MCS) and physical component summary (SF-36 PCS) scores were retrospectively calculated and used as patient-reported outcome. The association among these outcomes and the different origin of neuropsychiatric events was obtained using multiple logistic regression analysis. Results The clinical status of 26.8% non-neuropsychiatric systemic lupus erythematosus events, 15.8% ischaemic neuropsychiatric systemic lupus erythematosus and 51.6% inflammatory neuropsychiatric systemic lupus erythematosus improved after re-assessment. Almost all SF-36 domains had a positive change at re-assessment in all groups independently of the origin of neuropsychiatric events. Neuropsychiatric systemic lupus erythematosus ( B = 0.502; p < 0.001) and especially inflammatory neuropsychiatric systemic lupus erythematosus ( B = 0.827; p < 0.001) had better clinical outcome, with change in disease activity being the only important predictor. The change in SF-36 MCS was also independently associated with neuropsychiatric systemic lupus erythematosus ( B = 5.783; p < 0.05) and inflammatory neuropsychiatric systemic lupus erythematosus ( B = 11.133; p < 0.001). Disease duration and change in disease activity were the only predictors in both cases. The change in SF-36 PCS was only negatively associated with age. Conclusion Inflammatory neuropsychiatric systemic lupus erythematosus events have better clinical outcome and meaningful improvement in SF-36 MCS than ischaemic neuropsychiatric systemic lupus erythematosus or non-neuropsychiatric systemic lupus erythematosus.

Randomized comparison of a multidisciplinary team care program with usual care in patients with systemic sclerosis.

OBJECTIVE: To compare the effectiveness of a multidisciplinary team care program with usual outpatient care in patients with systemic sclerosis (SSc; scleroderma). METHODS: We performed a randomized controlled trial comparing a 12-week multidisciplinary team care program (1 day per week; individual treatments, group exercises, and group education) with outpatient clinic care. Outcome measures included the Hand Mobility in Scleroderma (HAMIS) test, grip strength, maximal mouth opening (MMO), 6-minute walk distance (6MWD), maximum aerobic capacity (VO(2max) ), Checklist Individual Strength 20 (CIS-20), SSc Health Assessment Questionnaire (HAQ), and Short Form 36 (SF-36), assessed at 0, 12, and 24 weeks. Statistical comparisons of change scores were done by analysis of covariance. RESULTS: Twenty-eight patients were assigned to the intervention group (mean age 53.9 years, 15 of 28 with diffuse SSc) and 25 were assigned to the control group (mean age 51.7 years, 15 of 25 with diffuse SSc). Twenty-five patients (89%) in the intervention group completed the treatment program. At 12 weeks, there was a significantly greater improvement in grip strength (2.2 versus -1.8 kg; P = 0.001), MMO (1.4 versus -0.9 mm; P = 0.011), 6MWD (42.8 versus 3.9 meters; P = 0.021), and HAQ score (-0.18 versus 0.13; P = 0.025) in the intervention group, whereas differences for the other outcome measures did not reach significance. At 24 weeks, the effect on grip strength persisted. CONCLUSION: In patients with SSc, a 12-week multidisciplinary day patient treatment program was more effective than regular outpatient care with respect to 6MWD, grip strength, MMO, and HAQ score, but not for VO(2max) , HAMIS test, CIS-20, SF-36, and visual analog scale for pain. This study provides a first step in quantifying the effect of a multidisciplinary team care program and warrants the conduct of further intervention studies.